Background Metabolic-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis
(NASH) are considered hepatic manifestations of metabolic syndrome for which no effective
pharmacological treatment exists. Dietary intervention with more than 10% weight loss
is effective but often fails due to low patient compliance. Alternatively, an increased
physical activity is considered to improve fatty liver disease even without weight
loss. The underlying mechanisms are unclear and cannot be studied in humans.
Methods Wistar rats were fed a standard or NASH-inducing high-fat diet with cholesterol and
fructose for 7 weeks. Both diet groups were divided into a sedentary and a running
exercise group.
Results Animals fed the high-fat diet gained more weight than standard diet-fed animals,
got glucose intolerant, and developed a liver pathology with steatosis, inflammation
and fibrosis similar to human NASH in the metabolic syndrome. While the endurance
training did not reduce body weight or improve the NASH activity score, it significantly
reduced the hepatic overload with dietary cholesterol and the resulting oxidative
stress. In addition, endurance training improved the diet-induced glucose intolerance,
possibly through exercise-induced generation of the hepatokine FGF21, which increased
fatty acid utilization in muscle.
Conclusion Endurance training failed to ameliorate diet-induced hepatic fatty liver disease
in rats but reduced hepatic cholesterol accumulation and oxidative damage of hepatocytes,
as well as high-fat diet-induced glucose intolerance possibly in part by production
of the hepatokine FGF21.
